Epithelial geometry regulates spindle orientation and progenitor fate during formation of the mammalian epidermis

Abstract
Data availability
Article and author information
Metrics

Abstract

The control of cell fate through oriented cell division is imperative for proper organ development. Basal epidermal progenitor cells divide parallel or perpendicular to the basement membrane to self-renew or produce differentiated stratified layers, but the mechanisms regulating the choice between division orientations are unknown. Using time-lapse imaging to follow divisions and fates of basal progenitors, we find that mouse embryos defective for the planar cell polarity (PCP) gene, Vangl2, exhibit increased perpendicular divisions and hyperthickened epidermis. Surprisingly, this is not due to defective Vangl2 function in the epidermis, but to changes in cell geometry and packing that arise from the open neural tube characteristic of PCP mutants. Through regional variations in epidermal deformation and physical manipulations, we find that local tissue architecture, rather than cortical PCP cues, regulates the decision between symmetric and stratifying divisions, allowing flexibility for basal cells to adapt to the needs of the developing tissue.

Data availability

All measured data are reported as their full distributions in the figures and supplements. Source data files with individual measurements are provided for all figures. Matlab codes for data analysis are provided in Source Code File 1.

Article and author information

Author details

Kimberly Box

Department of Molecular Biology, Princeton University, Princeton, United States

Competing interests
The authors declare that no competing interests exist.
Bradley W Joyce

Department of Molecular Biology, Princeton University, Princeton, United States

Competing interests
The authors declare that no competing interests exist.
Danelle Devenport

Department of Molecular Biology, Princeton University, Princeton, United States

For correspondence
danelle@princeton.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5464-259X

Funding

National Institutes of Health (R01AR068320)

Danelle Devenport

National Institutes of Health (T32GM007388)

Kimberly Box

National Institutes of Health (AR8472471)

Kimberly Box
Danelle Devenport

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All procedures involving animals were approved by Princeton University'sInstitutional Animal Care and Use Committee (IACUC) under protocol #1867. Mice were housed in an AALAC-accredited facility in accordance with the Guide for the Care and Use of Laboratory Animals. This study was compliant with all relevant ethical regulations regarding animal research.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.